Cephalosporins in pregnancy

Among all classes of antibacterial drugs intended for the treatment of inflammatory diseases caused by pathogenic and opportunistic microbes, cephalosporins in pregnancy are prescribed by doctors most often because these antibiotics cause fewer side effects and are not teratogenic (unlike antibiotics-aminoglycosides, lincosamides and fluoroquinolones ).

In this case, semisynthetic cephalosporins of the second and third generations are used in the treatment of pregnant women, which are also active against gram-negative bacteria and have a weaker toxic effect on the kidneys working during the period of bearing the child with increased stress.

However, in any case, cephalosporins are used during pregnancy solely for the purpose of the attending physician, who assesses the patient's condition and decides that it is impossible to cope with the infection without antibiotics.

[1], [2], [3], [4], [5], [6], [7]

Indications of the cephalosporins in pregnancy

Although the absolute safety of the use of cephalosporins during pregnancy is clinically insufficiently tested, these antibacterial drugs can be prescribed for pregnant women with infectious inflammation: ENT and respiratory tract (tonsillitis, pharyngitis, otitis, sinusitis, bronchitis, pleurisy and pneumonia); organs of the abdominal cavity and small pelvis (endometritis); genital tract (chlamydia, gonorrhea, cervicitis, etc.); urinary tract and kidney (cystitis, urethritis, nephritis, pyelonephritis); biliary tract (cholangitis); joints and periarticular tissues; pustular lesions of the skin (streptoderma, erysipelas, etc.).

Cephalosporins are very effective in the treatment of nosocomial infections, bacterial meningitis (caused by pneumonia and meningococci) and endocarditis, as well as during infection with salmonella, peritonitis and sepsis.

Here are some names of cephalosporins used during pregnancy:

• Cefuroxime (Cefuroxime axetil, Cefumax, Ketotsef, Novocef, Zinatsef, Zinnat and other synonyms);
• Cefotaxime (Cefosin, Cefanthral, Kefotex, Claforan, Klafotaxim, Talcef, etc.);
• Ceftriaxone (Cefaxone, Cefatrine, Betasporin, Lifaxon, Longacef, Rocefin);
• Cefixime (Cefix, Cephoral, Loprax, Suprax, Panzef).

[8], [9], [10], [11], [12]

Release form

The preparations mentioned in the review have the following forms of release:

Cefuroxime - tablets (125, 250 and 500 mg each); Granules for the preparation of a suspension (in vials or sachets); powder for solution for injection (in bottles of 250, 750 and 1500 mg).

Cefotaxime and Ceftriaxone - powder for the preparation of parenteral solution (in vials of 0.25-2 g).

Cefixime - capsules (100, 200 and 400 mg each); powder for suspension and ready-made suspension for oral administration (in 5 ml vials).

[13], [14], [15], [16], [17], [18], [19]

Pharmacodynamics

Like all beta-lactam antibiotics, cephalosporins in pregnancy (as well as preparations of the cephalosporins group used outside this state) have a bactericidal effect on the causative agents of infectious inflammations, the essence of which is the disruption of the synthesis of oligopeptide components and the crosslinking of peptidoglycan, the main substance of the murein wall of the bacterial cell. A change in the structural integrity of the cell membranes leads to lysis and death of cells of microorganisms: streptococci, staphylococci (except Staphylococcus aureus resistant Staphylococcus aureus strains resistant to penicillin), clostridia, erchorichia, protea, gonococci, mycoplasma, chlamydia, fusobacteria, bacteroides.

However, cephalosporins do not affect the causative agents of pseudomembrane enterocolitis -Clostridium difficile; pseudomonas, listeria monocytogenes, gastrointestinal Campylobacter spp., Legionella spp.

[20], [21], [22], [23], [24], [25], [26]

Pharmacokinetics

Parenteral administration of Cefuroxime after 25-45 minutes creates bacteria-killing concentrations in sputum, mucosa of the respiratory tract, cerebrospinal fluid and intercellular fluid in the tissues of internal organs, providing a therapeutic effect within 5-8. The drug binds to plasma proteins by no more than 50% and is not transformed in the liver; is excreted from the body by the kidneys (up to 90% - unchanged). The use of tablets Cefuroxime increases the time before the onset of action of the drug by almost 3.5 and extends the half-life to 12 hours.

The binding of the antibiotic Cefotaxime to plasma proteins is lower (on average about 35%), but the concentration required for treatment remains in the blood for 12 hours. This drug passes through the BBB. Metabolism is carried out by hepatic enzymes, with one-third of the cleavage products being active against bacteria. Cefotaxime is eliminated by the kidneys and partly by the intestine, with a half-life in the range of 1-2.5 hours.

The preparation ceftriaxone - due to rapid absorption, high degree of binding to plasma proteins (up to 90-95%) and 100% bioavailability - after intramuscular injection reaches a maximum concentration on average 2.5 hours, accumulating in tissues and interstitial liquids and liquor with subsequent administrations. About 45-55% of the drug is excreted from the body without changes, excretion with urine and partly with bile; the half-life lasts up to 8-9 hours.

Absorption is absorbed by cefixime after taking capsules or suspension is fast enough, but the bioavailability of this drug is about 40%, and the highest concentration in blood plasma is observed 4 hours after use. The main part of Cephixime is eliminated by the kidneys with a half-life of about 3.5 hours.

[27], [28], [29], [30], [31], [32], [33]

Dosing and administration

The cephalosporin antibiotics included in this review are used as follows:

Cefuroxime in tablets is prescribed by 0.25-0.5 g every 12 hours (during meals), a 10-day course. With pneumonia, the drug is used in the form of intramuscular injections - twice a day for 1.5 g for two to three days, after which they switch to the tablet preparation, taking another 5-7 days twice a day for 0.5 g.

Cefotaxime is administered as a vein, and in the muscle - three to four times a day at a daily dose in the range of 3-8 g (the specific dosage is determined by the doctor).

The daily dose of Ceftriaxone for injection is lower and ranges from one to two grams (divided into two injections per day).

Capsules Cefimxine pregnant can be prescribed to 200 mg twice a day.

[41], [42]

Contraindications

Antibiotics-cephalosporins are contraindicated in patients with a history of severe immediate allergic reactions (urticaria, anaphylactic shock, interstitial nephritis, etc.).

It is not recommended to use drugs of this pharmacological group in the presence of an anamnesis of enteritis, ulcerative colitis, functional liver failure, difficult to stop bleeding (associated with hypoprothrombinemia).

Contraindicated cephalosporins in the early stages of pregnancy (up to 4-5 months) - preparations of the first generation (Cefazolin, Cefalexin, Cefradin, etc.), as well as the third generation of cephalosporins - Ceftriaxone (Cefaxon, Cefatrine, Betasporin and other trade names ).

[34], [35], [36], [37], [38], [39]

Side effects of the cephalosporins in pregnancy

The main side effects of cephalosporins during pregnancy are manifested as:

• epidermal eruptions like dermatitis, purpura;
• leukopenia, thrombocytopenia, eosinophilia, thrombocytosis;
• fever, hyperhidrosis and anaphylactic reactions;
• general weakness and rapid fatigue;
• nausea, dry mouth, vomiting, flatulence, diarrhea, digestive disorders, abdominal pain;
• increased levels of bilirubin, hepatic transaminases and alkaline phosphatase in the blood;
• increased levels of urea and creatinine in the blood;
• the formation of gallstones.

[40]

Overdose

An overdose of antibiotic-cephalosporins can cause an increase in side effects, primarily nausea and diarrhea. There is a high probability of cramps. It is recommended to reduce the dose and use symptomatic.

[43], [44], [45], [46], [47]

Interactions with other drugs

The use of cephalosporin antibiotics simultaneously with non-steroidal anti-inflammatory drugs, including acetylsalicylic acid, increases the negative effect of antimicrobial drugs on the kidneys.

You can not combine cephalosporins during pregnancy with antibacterial drugs of other groups, for example, with aminoglycosides.

[48], [49], [50], [51], [52], [53], [54]

Storage conditions

These antibiotic cephalosporin series should be stored in a dark place at a temperature of up to + 25 ° C, and prepared emulsions for ingestion in the refrigerator (no longer than 7 days).

[55], [56], [57], [58], [59], [60], [61]

Shelf life

The shelf life of drugs in a sealed package is 24 months.

[62], [63], [64], [65], [66], [67]